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Background: Chimeric antigen receptor T- Cell (CAR-T) immunotherapy has been a breakthrough treatment for various hematological malignancies. However, cardiotoxicities such as new-onset heart failure, arrhythmia, acute coronary syndrome and cardiovascular death occur in 10-15% of patients treated with CAR-T. This study aims to investigate the changes in cardiac and inflammatory biomarkers in CAR-T therapy to determine the role of pro-inflammatory cytokines., Methods: In this observational study, ninety consecutive patients treated with CAR-T underwent baseline cardiac investigation with electrocardiogram (ECG), transthoracic echocardiogram (TTE), troponin-I, and B-type natriuretic peptide (BNP). Follow-up ECG, troponin-I and BNP were obtained five days post- CAR-T. In a subset of patients (N = 53), serum inflammatory cytokines interleukin (IL)-2, IL-6, IL-15, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and angiopoietin 1 & 2 were tested serially, including baseline and daily during hospitalization. Adverse cardiac events were defined as new-onset cardiomyopathy/heart failure, acute coronary syndrome, arrhythmia and cardiovascular death., Results: Eleven patients (12%) had adverse cardiac events (one with new-onset cardiomyopathy and ten with new-onset atrial fibrillation). Adverse cardiac events appear to have occurred among patients with advanced age (77 vs. 66 years; p = 0.002), higher baseline creatinine (0.9 vs. 0.7 mg/dL; 0.007) and higher left atrial volume index (23.9 vs. 16.9mL/m 2 ; p = 0.042). Day 5 BNP levels (125 vs. 63pg/mL; p = 0.019), but not troponin-I, were higher in patients with adverse cardiac events, compared to those without. The maximum levels of IL-6 (3855.0 vs. 254.0 pg/mL; p = 0.021), IFN-γ (474.0 vs. 48.8pg/mL; p = 0.006) and IL-15 (70.2 vs. 39.2pg/mL; p = 0.026) were also higher in the adverse cardiac events group. However, cardiac and inflammatory biomarker levels were not associated with cardiac events. Patients who developed cardiac events did not exhibit worse survival compared to patients without cardiac events (Log-rank p = 0.200)., Conclusion: Adverse cardiac events, predominantly atrial fibrillation, occur commonly after CAR-T (12%). The changes in serial inflammatory cytokine after CAR-T in the setting of adverse cardiac events suggests pro-inflammation as a pathophysiology and require further investigation for their role in adverse cardiac events., Tweet Brief Handle: CAR-T related Cardiotoxicity has elevated cardiac and inflammatory biomarkers. #CARTCell #CardioOnc #CardioImmunology., (© 2023. The Author(s).)

Background: Heart failure with preserved ejection fraction (HFpEF) is a syndrome with a heterogeneous cluster of causes, including non-resolving inflammation, endothelial dysfunction, and multi-organ defects. The present study's objective was to identify novel predictors of HFpEF., Methods: The study analyzed the Multi-Ethnic Study of Atherosclerosis (MESA) to assess the association of specific markers of inflammation with new onset of HFpEF (interleukin-2 [IL-2], matrix metalloproteinase 3 [MMP3], large low-density lipoprotein cholesterol [LDL-C], and medium high-density lipoprotein cholesterol [HDL-C]). The study included men and women 45 to 84 years of age without cardiovascular disease at baseline. The primary outcome was the multivariate association of the hypothesized markers of inflammation with new-onset of HFpEF versus participants without new-onset heart failure. Participants with missing data were excluded., Results: The present analysis included 6814 participants, 53% female, with a mean age of 62 years. Among the entire cohort, HFpEF was diagnosed in 151 (2.2%) participants and heart failure with reduced ejection fraction (HFrEF) was diagnosed in 146 (2.1%) participants. Participants were followed for the outcome of heart failure for a median 13.9 years. Baseline IL-2 was available for 2861 participants. The multivariate analysis included 2792 participants. Of these, 2668 did not develop heart failure, 62 developed HFpEF, 47 developed HFrEF, and 15 developed unclassified heart failure. In the multivariate regression model, IL-2 was associated with new-onset HFpEF (OR, 1.00058; 95% confidence interval, 1.00014 to 1.00102, p = 0.009) but not new-onset HFrEF. In multivariate analysis, MMP3, large LDL-C, and medium HDL-C were not associated with HFpEF or HFrEF., Conclusion: These findings portend IL-2 as an important component of suboptimal inflammation in the pathogenesis of HFpEF., (© 2022. The Author(s).)

Background: Decision thresholds play important role in medical decision-making. Individual decision-making differences may be attributable to differences in subjective judgments or cognitive processes that are captured through the decision thresholds. This systematic scoping review sought to characterize the literature on non-expected utility decision thresholds in medical decision-making by identifying commonly used theoretical paradigms and contextual and subjective factors that inform decision thresholds. Methods: A structured search designed around three concepts—individual decision-maker, decision threshold, and medical decision—was conducted in MEDLINE (Ovid) and Scopus databases from inception to July 2023. ProQuest (Dissertations and Theses) database was searched to August 2023. The protocol, developed a priori, was registered on Open Science Framework and PRISMA-ScR guidelines were followed for reporting on this study. Titles and abstracts of 1,618 articles and the full texts for the 228 included articles were reviewed by two independent reviewers. 95 articles were included in the analysis. A single reviewer used a pilot-tested data collection tool to extract study and author characteristics, article type, objectives, theoretical paradigm, contextual or subjective factors, decision-maker, and type of medical decision. Results: Of the 95 included articles, 68 identified a theoretical paradigm in their approach to decision thresholds. The most common paradigms included regret theory, hybrid theory, and dual processing theory. Contextual and subjective factors that influence decision thresholds were identified in 44 articles. Conclusions: Our scoping review is the first to systematically characterizes the available literature on decision thresholds within medical decision-making. This study offers an important characterization of the literature through the identification of the theoretical paradigms for non-expected utility decision thresholds. Moreover, this study provides insight into the various contextual and subjective factors that have been documented within the literature to influence decision thresholds, as well as these factors juxtapose theoretical paradigms. [ABSTRACT FROM AUTHOR]

Background: Random-pattern skin flaps are commonly used to repair skin tissue defects in surgical tissue reconstruction. However, flap necrosis in the distal area due to ischemia injury is still challenging for its applications in plastic surgery. The complications of diabetes will further increase the risk of infection and necrosis. Methods: This study induced type 2 diabetes mellitus (T2DM) rats with a high-fat diet and STZ. The survival rate of the skin flap was observed by adding inorganic sodium nitrate to drinking water. Histology and immunohistochemistry were used to detect the damage to the skin flap. The nitrate content was measured by total nitric oxide and nitrate/nitrite parameter assay. Dihydroethidium and malondialdehyde (MDA) assays were used to value oxidative stress. Rat colon feces were collected for 16s rRNA gene sequence. Results: Our studies showed that nitrate administration leads to anti-obesity and anti-diabetic effects. Nitrate directly increased the survival area of skin flaps in diabetic rats and mean blood vessel density by enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. The 16s rRNA sequence revealed that nitrate may regulate the homeostasis of the gut microbiota and re-store energy metabolism. Conclusion: Dietary nitrate has been shown to maintain the homeostasis of oxidative stress and gut microbiota to promote flap survival in rats with T2DM. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is considered a terminal illness with a five-year survival rate of about 16%. Informed decision-making related to the management of a disease requires accurate prognosis of the disease with or without treatment. Despite the significance of disease prognosis in clinical decision-making, systematic assessment of prognosis in patients with lung cancer without treatment has not been performed. We conducted a systematic review and meta-analysis of the natural history of patients with confirmed diagnosis of lung cancer without active treatment, to provide evidence-based recommendations for practitioners on management decisions related to the disease. Specifically, we estimated overall survival when no anticancer therapy is provided., Methods: Relevant studies were identified by search of electronic databases and abstract proceedings, review of bibliographies of included articles, and contacting experts in the field. All prospective or retrospective studies assessing prognosis of lung cancer patients without treatment were eligible for inclusion. Data on mortality was extracted from all included studies. Pooled proportion of mortality was calculated as a back-transform of the weighted mean of the transformed proportions using the random-effects model. To perform meta-analysis of median survival, published methods were used to pool the estimates as mean and standard error under the random-effects model. Methodological quality of the studies was examined., Results: Seven cohort studies (4,418 patients) and 15 randomized controlled trials (1,031 patients) were included in the meta-analysis. All studies assessed mortality without treatment in patients with non-small cell lung cancer (NSCLC). The pooled proportion of mortality without treatment in cohort studies was 0.97 (95% CI: 0.96 to 0.99) and 0.96 in randomized controlled trials (95% CI: 0.94 to 0.98) over median study periods of eight and three years, respectively. When data from cohort and randomized controlled trials were combined, the pooled proportion of mortality was 0.97 (95% CI: 0.96 to 0.98). Test of interaction showed a statistically non-significant difference between subgroups of cohort and randomized controlled trials. The pooled mean survival for patients without anticancer treatment in cohort studies was 11.94 months (95% CI: 10.07 to 13.8) and 5.03 months (95% CI: 4.17 to 5.89) in RCTs. For the combined data (cohort studies and RCTs), the pooled mean survival was 7.15 months (95% CI: 5.87 to 8.42), with a statistically significant difference between the two designs. Overall, the studies were of moderate methodological quality., Conclusion: Systematic evaluation of evidence on prognosis of NSCLC without treatment shows that mortality is very high. Untreated lung cancer patients live on average for 7.15 months. Although limited by study design, these findings provide the basis for future trials to determine optimal expected improvement in mortality with innovative treatments.

Background: Stereotactic ablative radiotherapy (SABR) is the standard treatment for medically inoperable early-stage non-small cell lung cancer (ES-NSCLC), but which patients benefit from stereotactic radiotherapy is unclear. The aim of this study was to analyze prognostic factors for early mortality. Methods: From August 2010 to 2022, 617 patients with medically inoperable, peripheral or central ES-NSCLC were treated with SABR at our institution. We retrospectively evaluated the data from 172 consecutive patients treated from 2018 to 2020 to analyze the prognostic factors associated with overall survival (OS). The biological effective dose was > 100 Gy10 in all patients, and 60 Gy was applied in 3–5 fractions for a gross tumor volume (GTV) + 3 mm margin when the tumor diameter was < 1 cm; 30–33 Gy was delivered in one fraction. Real-time tumor tracking or an internal target volume approach was applied in 96% and 4% of cases, respectively. In uni- and multivariate analysis, a Cox model was used for the following variables: ventilation parameter FEV1, histology, age, T stage, central vs. peripheral site, gender, pretreatment PET, biologically effective dose (BED), and age-adjusted Charlson comorbidity index (AACCI). Results: The median OS was 35.3 months. In univariate analysis, no correlation was found between OS and ventilation parameters, histology, PET, or centrality. Tumor diameter, biological effective dose, gender, and AACCI met the criteria for inclusion in the multivariate analysis. The multivariate model showed that males (HR 1.51, 95% CI 1.01–2.28; p = 0.05) and AACCI > 5 (HR 1.56, 95% CI 1.06–2.31; p = 0.026) were significant negative prognostic factors of OS. However, the analysis of OS showed that the significant effect of AACCI > 5 was achieved only after 3 years (3-year OS 37% vs. 56%, p = 0.021), whereas the OS in one year was similar (1-year OS 83% vs. 86%, p = 0.58). Conclusion: SABR of ES-NSCLC with precise image guidance is feasible for all medically inoperable patients with reasonable performance status. Early deaths were rare in our real-life cohort, and OS is clearly higher than would have been expected after best supportive care. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease affecting 30% of the world's population and is often associated with metabolic disorders such as metabolic syndrome, type 2 diabetes (T2D), and cardiovascular disease. This review is an update of the Brazilian Diabetes Society (Sociedade Brasileira de Diabetes [SBD]) evidence-based guideline for the management of MASLD in clinical practice. Methods: The methodology was published previously and was defined by the internal institutional steering committee. The SBD Metabolic Syndrome and Prediabetes Department drafted the manuscript, selecting key clinical questions for a narrative review using MEDLINE via PubMed with the MeSH terms [diabetes] and [fatty liver]. The best available evidence was reviewed, including randomized clinical trials (RCTs), meta-analyses, and high-quality observational studies related to MASLD. Results and conclusions: The SBD Metabolic Syndrome and Prediabetes Department formulated 9 recommendations for the management of MASLD in people with prediabetes or T2D. Screening for the risk of advanced fibrosis associated with MASLD is recommended in all adults with prediabetes or T2D. Lifestyle modification (LSM) focusing on a reduction in body weight of at least 5% is recommended as the first choice for these patients. In situations where LSMs are insufficient to achieve weight loss, the use of anti-obesity medications is recommended for those with a body mass index (BMI) ≥ 27 kg/m2. Pioglitazone and glucagon-like peptide-1 receptor agonists (GLP-1RA) monotherapy are the first-line pharmacological treatments for steatohepatitis in people with T2D, and sodium–glucose cotransporter-2 (SGLT2) inhibitors may be considered in this context. The combination of these agents may be considered in the treatment of steatohepatitis and/or fibrosis, and bariatric surgery should be considered in patients with a BMI ≥ 35 kg/m2, in which the combination of LSM and pharmacotherapy has not been shown to be effective in improving MASLD. [ABSTRACT FROM AUTHOR]

Background: No-show to medical appointments has significant adverse effects on healthcare systems and their clients. Using machine learning to predict no-shows allows managers to implement strategies such as overbooking and reminders targeting patients most likely to miss appointments, optimizing the use of resources. Methods: In this study, we proposed a detailed analytical framework for predicting no-shows while addressing imbalanced datasets. The framework includes a novel use of z-fold cross-validation performed twice during the modeling process to improve model robustness and generalization. We also introduce Symbolic Regression (SR) as a classification algorithm and Instance Hardness Threshold (IHT) as a resampling technique and compared their performance with that of other classification algorithms, such as K-Nearest Neighbors (KNN) and Support Vector Machine (SVM), and resampling techniques, such as Random under Sampling (RUS), Synthetic Minority Oversampling Technique (SMOTE) and NearMiss-1. We validated the framework using two attendance datasets from Brazilian hospitals with no-show rates of 6.65% and 19.03%. Results: From the academic perspective, our study is the first to propose using SR and IHT to predict the no-show of patients. Our findings indicate that SR and IHT presented superior performances compared to other techniques, particularly IHT, which excelled when combined with all classification algorithms and led to low variability in performance metrics results. Our results also outperformed sensitivity outcomes reported in the literature, with values above 0.94 for both datasets. Conclusion: This is the first study to use SR and IHT methods to predict patient no-shows and the first to propose performing z-fold cross-validation twice. Our study highlights the importance of avoiding relying on few validation runs for imbalanced datasets as it may lead to biased results and inadequate analysis of the generalization and stability of the models obtained during the training stage. [ABSTRACT FROM AUTHOR]

Background: Women at risk of gestational diabetes mellitus (GDM) need preventative interventions. Objective: To evaluate targeted interventions before and during pregnancy for women identified as being at risk of developing GDM. Methods: Systematic review and meta-analysis conducted following PRISMA guidelines. MEDLINE, EMBASE and the Cochrane Library in addition to reference and citation lists were searched to identify eligible randomised controlled trials (RCTs) utilising risk stratification during the preconception period or in the first/early second trimester. Screening and data extraction were carried out by the authors independently. Quality assessment was conducted based on the Cochrane risk-of-bias tool. Random effects meta-analysis and narrative synthesis were performed. Results: Eighty-four RCTs were included: two during preconception and 82 in pregnancy, with a pooled sample of 22,568 women. Interventions were behavioural (n = 54), dietary supplementation (n = 19) and pharmacological (n = 11). Predictive factors for risk assessment varied; only one study utilised a validated prediction model. Gestational diabetes was reduced in diet and physical activity interventions (risk difference − 0.03, 95% CI 0.06, − 0.01; I2 58.69%), inositol (risk difference − 0.19, 95% CI 0.33, − 0.06; I2 92.19%), and vitamin D supplements (risk difference − 0.16, 95% CI 0.25, − 0.06; I2 32.27%). Subgroup analysis showed that diet and physical activity interventions were beneficial in women with ≥ 2 GDM risk factors (risk difference − 0.16, 95% CI 0.25, − 0.07; I2 11.23%) while inositol supplementation was effective in women with overweight or obesity (risk difference − 0.17, 95% CI 0.22, − 0.11; I2 0.01%). Effectiveness of all other interventions were not statistically significant. Conclusions: This review provides evidence that interventions targeted at women at risk of GDM may be an effective strategy for prevention. Further studies using validated prediction tools or multiple risk factors to target high-risk women for intervention before and during pregnancy are warranted. [ABSTRACT FROM AUTHOR]

Background: Torpedo maculopathy (TM) is a rare, congenital condition characterized by an oval-shaped, chorioretinal lesion in the temporal macula of unknown etiology. To our knowledge, the longest reported follow-up of TM is 5 years. Herein we report 10 years of follow-up on two patients with TM to further characterize the long-term natural history of the condition. Case reports: Two patients with torpedo maculopathy were examined at baseline and then again at 5 years and 10 years from baseline. Eyes were evaluated using color fundus photography, automated perimetry, fundus autofluorescence and spectral domain optical coherence tomography. Visual function of both patients remained stable throughout the observation period. In case 1, there was no evidence of change in lesion morphology over the 10 year observation period. Case 2 showed progression of cystic degeneration of the neurosensory retina within the torpedo lesion. Case 1 reported a history of supernumerary teeth and underwent gene sequence with deletion/duplication analyses of the APC gene but no clinically significant variants were detected. Conclusions: Our findings support the position that TM is a nonprogressive condition with long-term stability of visual function. Genetic analysis of case 1 failed to detect any association with Gardner syndrome. [ABSTRACT FROM AUTHOR]

Background: No-show appointments pose a significant challenge for healthcare providers, particularly in rural areas. In this study, we developed an evidence-based predictive model for patient no-shows at the Marshfield Clinic Health System (MCHS) rural provider network in Wisconsin, with the aim of improving overbooking approaches in outpatient settings and reducing the negative impact of no-shows in our underserved rural patient populations. Methods: Retrospective data (2021) were obtained from the MCHS scheduling system, which included 1,260,083 total appointments from 263,464 patients, as well as their demographic, appointment, and insurance information. We used descriptive statistics to associate variables with show or no-show status, logistic regression, and random forests utilized, and eXtreme Gradient Boosting (XGBoost) was chosen to develop the final model, determine cut-offs, and evaluate performance. We also used the model to predict future no-shows for appointments from 2022 and onwards. Results: The no-show rate was 6.0% in both the train and test datasets. The train and test datasets both yielded 5.98. Appointments scheduled further in advance (> 60 days of lead time) had a higher (7.7%) no-show rate. Appointments for patients aged 21–30 had the highest no-show rate (11.8%), and those for patients over 60 years of age had the lowest (2.9%). The model predictions yielded an Area Under Curve (AUC) of 0.84 for the train set and 0.83 for the test set. With the cut-off set to 0.4, the sensitivity was 0.71 and the positive predictive value was 0.18. Model results were used to recommend 1 overbook for every 6 at-risk appointments per provider per day. Conclusions: Our findings demonstrate the feasibility of developing a predictive model based on administrative data from a predominantly rural healthcare system. Our new model distinguished between show and no-show appointments with high performance, and 1 overbook was advised for every 6 at-risk appointments. This data-driven approach to mitigating the impact of no-shows increases treatment availability in rural areas by overbooking appointment slots on days with an elevated risk of no-shows. [ABSTRACT FROM AUTHOR]

Background: Institutional review boards (IRBs) are formally designated to review, approve, and monitor biomedical research. They are responsible for ensuring that researchers comply with the ethical guidelines concerning human research participants. Given that IRBs might face different obstacles that cause delays in their processes or conflicts with investigators, this study aims to report the functions, roles, resources, and review process of IRBs in Saudi Arabia. Method: This was a cross-sectional self-reported survey conducted from March 2021 to March 2022. The survey was sent to 53 IRB chairpersons and the administration directors (or secretary) across the country through email after receiving verbal consent. The validated survey consisted of eight aspects: (a) organizational aspects, (b) membership and educational training, (c) submission arrangements and materials, (d) minutes, (e) review procedures, (f) communicating a decision, (g) continuing review, and (h) research ethics committee (REC) resources. A total of 200 points indicated optimal IRB functions. Results: Twenty-six IRBs across Saudi Arabia responded to the survey. Overall, the IRBs in this study scored a total of 150/200 of the points on the self-assessment tool. Relatively newer IRBs (established less than ten years ago) conducted meetings at least once in a month, had annual funding, had more balanced gender representation, tended to score higher than older IRBs. The organizational aspect score was the lowest among all items in the survey (14.3 score difference, p-value < 0.01). The average turnaround time for expedited research from proposal submission to final decision was 7 days, while it was 20.5 days for the full committee review. Conclusion: Saudi IRBs performed generally well. However, there is room for focused improvement with respect to extra resources and organizational issues that require closer evaluation and guidance from the regulatory bodies. [ABSTRACT FROM AUTHOR]

Cancer-associated anemia promotes tumor progression, leads to poor quality of life in patients with cancer, and even obstructs the efficacy of immune checkpoint inhibitors therapy. However, the precise mechanism for cancer-associated anemia remains unknown and the feasible strategy to target cancer-associated anemia synergizing immunotherapy needs to be clarified. Here, we review the possible mechanisms of cancer-induced anemia regarding decreased erythropoiesis and increased erythrocyte destruction, and cancer treatment-induced anemia. Moreover, we summarize the current paradigm for cancer-associated anemia treatment. Finally, we propose some prospective paradigms to slow down cancer-associated anemia and synergistic the efficacy of immunotherapy. 5auGJQBTvo5Tcx3eVUSnH7 Video Abstract [ABSTRACT FROM AUTHOR]

Background: Seafood is a good source of essential fatty acids which has a presumably beneficial effect on developing embryos and fetuses, although it is also a source of contaminants. In this context, pregnant women are faced with conflicting reports on the risk and benefits of seafood consumption. This study aims to assess whether the consumption of seafood during pregnancy was associated with fetal growth in an inland city in China. Methods: This study included 10,179 women who delivered a singleton live birth in Lanzhou, China. Seafood consumption was assessed using a Food Frequency Questionnaire. Maternal data including birth outcomes and maternal complications information is extracted from the medical records. Associations between seafood consumption and fetal growth indicators were analyzed using multiple linear regression and multiple logistic regression. Results: There was a positive association between total seafood consumption and birth weight (β = 0.027, 95%CI:0.030–0.111) but no association concerning birth length or head circumference. Seafood consumption was associated with decreased risk of low birth weight (OR = 0.575, 95% CI: 0.480, 0.689). The frequency of seafood consumption during pregnancy showed a trend toward a positive association with low birth weight. Significantly reduced rates of low birth weight were found in women who consumed more than 75 g of seafood/week during pregnancy as compared to women with no or very low intakes (P for trend 0.021). A significant interaction was observed between pre-pregnancy BMI and seafood consumption on birth weight among underweight women, but not among overweight women. Gestational weight gain partially mediated the association between seafood consumption and birth weight. Conclusions: Maternal seafood consumption was associated with decreased risk of low birth weight and increased birth weight. This association was mainly driven by freshwater fish and shellfish. These results further corroborate the present dietary recommendation to the Chinese Nutrition Society for pregnant women, especially those with underweight pre-pregnancy BMI and inadequate GWG. In addition, our findings provide implications for future interventions to improve seafood consumption among pregnant women to prevent low birth weight babies in the inland city in China. [ABSTRACT FROM AUTHOR]

Background: Microwave ablation (MWA) via ultrasound guidance is an important tool in the treatment of liver metastases. The most common postoperative complications are abdominal hemorrhage and bile leakage, whereas thrombosis in the suprahepatic inferior vena cava (IVC) is very rare, and clinical management is very difficult when the head end of the thrombus reaches the right atrium. Case presentation: This is a case report of a 52-year-old man with hepatic metastasis 21 months after radical resection of rectal cancer. After chemotherapy combined with targeted therapy, metastasis in segment IV (S4) of the liver was treated with microwave ablation. Two months after treatment, the hepatic metastasis in S4 showed a microwave ablation zone on MRI.Enhanced MRI showed venous thrombosis located in the left hepatic vein and IVC, and the head of the thrombus reached the right atrium. After two weeks of anticoagulation and thrombolytic treatment, the follow-up MRI showed that the venous thrombus had nearly disappeared. Conclusion: When liver metastases are close to the hepatic vein, clinicians should pay attention to the occurrence of hepatic vein and IVC thrombosis following MWA; through early diagnosis and anticoagulation, pulmonary thromboembolism (PTE) can be minimized. [ABSTRACT FROM AUTHOR]

Over the past decade, targeted therapy for oncogene-driven NSCLC and immune checkpoint inhibitors for non-oncogene-driven NSCLC, respectively, have greatly improved the survival and quality of life for patients with unresectable NSCLC. Increasingly, these biomarker-guided systemic therapies given before or after surgery have been used in patients with early-stage NSCLC. In March 2022, the US FDA granted the approval of neoadjuvant nivolumab and chemotherapy for patients with stage IB-IIIA NSCLC. Several phase II/III trials are evaluating the clinical efficacy of various neoadjuvant immune checkpoint inhibitor combinations for non-oncogene-driven NSCLC and neoadjuvant molecular targeted therapies for oncogene-driven NSCLC, respectively. However, clinical application of precision neoadjuvant treatment requires a paradigm shift in the biomarker testing and multidisciplinary collaboration at the diagnosis of early-stage NSCLC. In this comprehensive review, we summarize the current diagnosis and treatment landscape, recent advances, new challenges in biomarker testing and endpoint selections, practical considerations for a timely multidisciplinary collaboration at diagnosis, and perspectives in emerging neoadjuvant precision systemic therapy for patients with resectable, early-stage NSCLC. These biomarker-guided neoadjuvant therapies hold the promise to improve surgical and pathological outcomes, reduce systemic recurrences, guide postoperative therapy, and improve cure rates in patients with resectable NSCLC. [ABSTRACT FROM AUTHOR]

Background: Artificial intelligence (AI) is increasingly used to support general practice in the early detection of disease and treatment recommendations. However, AI systems aimed at alleviating time-consuming administrative tasks currently appear limited. This scoping review thus aims to summarize the research that has been carried out in methods of machine learning applied to the support and automation of administrative tasks in general practice. Methods: Databases covering the fields of health care and engineering sciences (PubMed, Embase, CINAHL with full text, Cochrane Library, Scopus, and IEEE Xplore) were searched. Screening for eligible studies was completed using Covidence, and data was extracted along nine research-based attributes concerning general practice, administrative tasks, and machine learning. The search and screening processes were completed during the period of April to June 2022. Results: 1439 records were identified and 1158 were screened for eligibility criteria. A total of 12 studies were included. The extracted attributes indicate that most studies concern various scheduling tasks using supervised machine learning methods with relatively low general practitioner (GP) involvement. Importantly, four studies employed the latest available machine learning methods and the data used frequently varied in terms of setting, type, and availability. Conclusion: The limited field of research developing in the application of machine learning to administrative tasks in general practice indicates that there is a great need and high potential for such methods. However, there is currently a lack of research likely due to the unavailability of open-source data and a prioritization of diagnostic-based tasks. Future research would benefit from open-source data, cutting-edge methods of machine learning, and clearly stated GP involvement, so that improved and replicable scientific research can be done. [ABSTRACT FROM AUTHOR]

Background: Lipocalin-2 (LCN2) has a critical effect on obesity as well as its associated comorbidities. The present study focused on analyzing serum LCN2 levels of obese patients with nonalcoholic fatty liver disease (NAFLD) and on determining relationship of hepatic steatosis improvement with LCN2 levels after laparoscopic sleeve gastrectomy (LSG). Methods: This work enrolled ninety patients with obesity and NAFLD. Twenty-three of them underwent LSG. Anthropometric and biochemical parameters and serum LCN2 levels were determined at baseline and those at 6-month post-LSG. Controlled attenuation parameter (CAP) measured by FibroScan was adopted for evaluating hepatic steatosis. Results: Among severe obesity patients, serum LCN2 levels were significantly increased (111.59 ± 51.16 ng/mL vs. 92.68 ± 32.68 ng/mL, P = 0.035). The CAP value was higher indicating higher liver fat content (360.51 ± 45.14 dB/m vs. 340.78 ± 45.02 dB/m, P = 0.044). With regard to surgical patients, liver function, glucose, and lipid levels were significantly improved after surgery. Serum LCN2 levels significantly decreased (119.74 ± 36.15 ng/mL vs. 87.38 ± 51.65 ng/mL, P = 0.001). Decreased CAP indicated a significant decrease in liver fat content (358.48 ± 46.13 dB/m vs. 260.83 ± 69.64 dB/m, P < 0.001). The decrease in LCN2 levels was significantly related to the reduced hepatic fat content and improvement in steatosis grade after adjusting for gender, age, and BMI decrease. Conclusions: Serum LCN2 levels are related to obesity and NAFLD. The decreased serum LCN2 levels could be an indicator of hepatic steatosis improvement. [ABSTRACT FROM AUTHOR]

Background: Yoga is a popular mind-body medicine frequently recommended to pregnant women. Gaps remain in our understanding of the core components of effective pregnancy yoga programmes. This systematic review and meta-analysis examined the characteristics and effectiveness of pregnancy yoga interventions, incorporating the FITT (frequency, intensity, time/duration and type) principle of exercise prescription. Methods: Nine electronic databases were searched: MEDLINE, PsycINFO, EMBASE, CINAHL, WHOLiS, AMED, ScieLo, ASSIA and Web of Science. Randomised control trials and quasi-experimental studies examining pregnancy yoga interventions were eligible. Covidence was used to screen titles, abstracts, and full-text articles. Outcomes of interest were stress, anxiety, depression, quality of life, labour duration, pain management in labour and mode of birth. The Cochrane Collaboration's Risk of Bias Assessment tool was used to assess methodological quality of studies and GRADE criteria (GRADEpro) evaluated quality of the evidence. Meta-analysis was performed using RevMan 5.3. Results: Of 862 citations retrieved, 31 studies met inclusion criteria. Twenty-nine studies with 2217 pregnant women were included for meta-analysis. Pregnancy yoga interventions reduced anxiety (SMD: -0.91; 95% CI: − 1.49 to − 0.33; p = 0.002), depression (SMD: -0.47; 95% CI: − 0.9 to − 0.04, P = 0.03) and perceived stress (SMD: -1.03; 95% CI: − 1.55 to − 0.52; p < 0.001). Yoga interventions also reduced duration of labour (MD = − 117.75; 95% CI − 153.80 to − 81.71, p < 0.001) and, increased odds of normal vaginal birth (OR 2.58; 95% CI 1.46–4.56, p < 0.001) and tolerance for pain. The quality of evidence (GRADE criteria) was low to very low for all outcomes. Twelve or more yoga sessions delivered weekly/bi-weekly had a statistically significant impact on mode of birth, while 12 or more yoga sessions of long duration (> 60 min) had a statistically significant impact on perceived stress. Conclusion: The evidence highlights positive effects of pregnancy yoga on anxiety, depression, perceived stress, mode of birth and duration of labour. Systematic review registration: PROSPERO, CRD42019119916. Registered on 11th January 2019. [ABSTRACT FROM AUTHOR]

Background: Medication adherence plays a pivotal role in achieving the desired treatment outcomes. The proportion of HIV patients on second-line antiretroviral therapy is becoming a growing public health concern. However, to date, little attention has been given to second-line antiretroviral medication adherence. Moreover, the association between health facility characteristics and medication adherence has yet not been tested. Thus, this research was conducted to determine the magnitude of medication adherence and examine the role of facility-level determinants among HIV patients on second-line ART. Methods: A cross-sectional study was conducted on 714 HIV patients on second-line therapy who were selected via systematic random sampling in twenty public health facilities. Medication adherence was measured using the six-item Simplified Medication Adherence Questionnaire (SMAQ) tool. Data were collected in a personal interview as well as document reviews. A multi-level binary logistic regression was used to uncover individual and facility-level determinants. The effect size was presented using an adjusted odds ratio (AOR), and statistical significance was declared at a P value less than 0.05. Results: The magnitude of optimal medication adherence among HIV patients on second-line antiretroviral therapy was 69.5% (65.9–72.7%). Medication adherence was positively associated with the use of adherence reminder methods [AOR = 3.37, (95% CI 2.03–5.62)], having social support [AOR = 1.11, (95% CI 1.02–1.23)], and not having clinical depression [AOR = 3.19, (95% CI 1.93–5.27). The number of adherence counselors [AOR = 1.20, (95% CI 1.04–1.40)], teamwork for enhanced adherence support [AOR = 1.82, (95% CI 1.01–3.42)], and caseloads at ART clinics were all significantly correlated with ARV medication adherence at the facility level. Conclusions: A large proportion of HIV patients on second-line antiretroviral therapy had adherence problems. Both facility-level and individual-level were linked with patient medication adherence. Thus, based on the identified factors, individual and system-level interventions should be targeted. [ABSTRACT FROM AUTHOR]

Background: There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and dietary-supplement treatments for ASD. Methods: We searched for randomized-controlled-trials (RCTs) with a minimum duration of seven days in ClinicalTrials.gov, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (from inception up to July 8, 2018), CENTRAL and PubMed (up to November 3, 2021). The co-primary outcomes were core symptoms (social-communication difficulties-SCD, repetitive behaviors-RB, overall core symptoms-OCS) measured by validated scales and standardized-mean-differences (SMDs). Associated symptoms, e.g., irritability/aggression and attention-deficit/hyperactivity disorder (ADHD) symptoms, dropouts and important side-effects, were investigated as secondary outcomes. Studies in children/adolescents and adults were analyzed separately in random-effects pairwise and network meta-analyses. Results: We analyzed data for 41 drugs and 17 dietary-supplements, from 125 RCTs (n = 7450 participants) in children/adolescents and 18 RCTs (n = 1104) in adults. The following medications could improve at least one core symptom domain in comparison with placebo: aripiprazole (k = 6 studies in analysis, SCD: SMD = 0.27 95% CI [0.09, 0.44], RB: 0.48 [0.26, 0.70]), atomoxetine (k = 3, RB:0.49 [0.18, 0.80]), bumetanide (k = 4, RB: 0.35 [0.09, 0.62], OCS: 0.61 [0.31, 0.91]), and risperidone (k = 4, SCM: 0.31 [0.06, 0.55], RB: 0.60 [0.29, 0.90]; k = 3, OCS: 1.18 [0.75, 1.61]) in children/adolescents; fluoxetine (k = 1, RB: 1.20 [0.45, 1.96]), fluvoxamine (k = 1, RB: 1.04 [0.27, 1.81]), oxytocin (k = 6, RB:0.41 [0.16, 0.66]) and risperidone (k = 1, RB: 0.97 [0.21,1.74]) in adults. There were some indications of improvement by carnosine, haloperidol, folinic acid, guanfacine, omega-3-fatty-acids, probiotics, sulforaphane, tideglusib and valproate, yet imprecise and not robust. Confidence in these estimates was very low or low, except moderate for oxytocin. Medications differed substantially in improving associated symptoms, and in their side-effect profiles. Limitations: Most of the studies were inadequately powered (sample sizes of 20–80 participants), with short duration (8–13 weeks), and about a third focused on associated symptoms. Networks were mainly star-shaped, and there were indications of reporting bias. There was no optimal rating scale measuring change in core symptoms. Conclusions: Some medications could improve core symptoms, although this could be likely secondary to the improvement of associated symptoms. Evidence on their efficacy and safety is preliminary; therefore, routine prescription of medications for the core symptoms cannot be recommended. Trial registration PROSPERO-ID CRD42019125317. [ABSTRACT FROM AUTHOR]

Background: Adolescent pregnancy is a major public health problem with significant medical, nutritional, social and economic risk for mothers and their infants. The purpose of this study was to determine prevalence and predictors of malnutrition among pregnant adolescents in Kore district, southern Ethiopia.Methods: Data were obtained from randomly selected consenting four hundred twenty five pregnant adolescents on March 2018 using interviewer-administered questionnaire and mid upper arm circumference (MUAC) measurement. A multivariable logistic regression analysis was used to identify the predictors of malnutrition in adolescent pregnancy.Results: The study showed that 26.4% of study participants were malnourished (MUAC < 22 cm). Not owning livestock (AOR = 1.67, 95% CI = 1.26-2.19), unintended pregnancy (AOR = 1.36, 95% CI = 1.08-1.65), excess physical work in pregnancy (AOR = 1.29, 95% CI = 1.02-1.62) and being in the second (AOR = 1.70, 95% CI = 1.09-2.65) or third (AOR = 1.99, 95% CI = 1.29-3.07) pregnancy trimester were positively associated with malnutrition risk. Improved dietary intake in pregnancy (AOR = 0.46, 95% CI = 0.33-0.63) and support perceived by adolescents in pregnancy (AOR = 0.59, 95% CI = 0.43-0.82) were negatively associated with malnutrition risk.Conclusion: More than one-quarter of the study population were malnourished. The information provides insight into the public health strategies to reduce malnutrition risk of the pregnant adolescents. Interventions aimed at improving socioeconomic status, dietary practice and physical work/activity through effective supports in pregnancy are recommended. [ABSTRACT FROM AUTHOR]

Background: The small tyrosine kinase inhibitors (TKIs) subversively altered the lung cancer treatments, but patients will inevitably face the therapy resistance and disease recurrence. We aim to explore the potential roles of non-coding RNAs in sensitizing the TKIs effects. Methods: Multiple cellular and molecular detections were applied to confirm the mechanistic regulations and intracellular connections. Results: We explored the specific gene features of candidates in association with resistance, and found that m6A controlled the stemness of EMT features through METTL3 and YTHDF2. The miR-146a/Notch signaling was sustained highly activated in a m6A dependent manner, and the m6A regulator of YTHDF2 suppressed TUSC7, both of which contributed to the resistant features. Functionally, the sponge type of TUSC7 regulation of miR-146a inhibited Notch signaling functions, and affected the cancer progression and stem cells' renewal in Erlotinib resistant PC9 cells (PC9ER) and Erlotinib resistant HCC827 cells (HCC827ER) cells. The Notch signaling functions manipulated the cMYC and DICER inner cytoplasm, and the absence of either cMYC or DICER1 lead to TUSC7 and miR-146a decreasing respectively, formed the closed circle to maintain the balance. Conclusion: PC9ER and HCC827ER cells harbored much more stem-like cells, and the resistance could be reversed by Notch signaling inactivation. The intrinsic miR-146 and TUSC7 levels are monitored by m6A effectors, the alternation of either miR-146 or TUSC7 expression could lead to the circling loop to sustain the new homeostasis. Further in clinics, the combined delivery of TKIs and Notch specific inhibitory non-coding RNAs will pave the way for yielding the susceptibility to targeted therapy in lung cancer. [ABSTRACT FROM AUTHOR]

Background: Brain-computer interfaces decode intentions directly from the human brain with the aim to restore lost functionality, control external devices or augment daily experiences. To combine optimal performance with wide applicability, high-quality brain signals should be captured non-invasively. Magnetoencephalography (MEG) is a potent candidate but currently requires costly and confining recording hardware. The recently developed optically pumped magnetometers (OPMs) promise to overcome this limitation, but are currently untested in the context of neural interfacing. Results: In this work, we show that OPM-MEG allows robust single-trial analysis which we exploited in a real-time 'mind-spelling' application yielding an average accuracy of 97.7%. Conclusions: This shows that OPM-MEG can be used to exploit neuro-magnetic brain responses in a practical and flexible manner, and opens up new avenues for a wide range of new neural interface applications in the future. [ABSTRACT FROM AUTHOR]

Background: The validity of observational studies and their meta-analyses is contested. Here, we aimed to appraise thousands of meta-analyses of observational studies using a pre-specified set of quantitative criteria that assess the significance, amount, consistency, and bias of the evidence. We also aimed to compare results from meta-analyses of observational studies against meta-analyses of randomized controlled trials (RCTs) and Mendelian randomization (MR) studies.Methods: We retrieved from PubMed (last update, November 19, 2020) umbrella reviews including meta-analyses of observational studies assessing putative risk or protective factors, regardless of the nature of the exposure and health outcome. We extracted information on 7 quantitative criteria that reflect the level of statistical support, the amount of data, the consistency across different studies, and hints pointing to potential bias. These criteria were level of statistical significance (pre-categorized according to 10-6, 0.001, and 0.05 p-value thresholds), sample size, statistical significance for the largest study, 95% prediction intervals, between-study heterogeneity, and the results of tests for small study effects and for excess significance.Results: 3744 associations (in 57 umbrella reviews) assessed by a median number of 7 (interquartile range 4 to 11) observational studies were eligible. Most associations were statistically significant at P < 0.05 (61.1%, 2289/3744). Only 2.6% of associations had P < 10-6, ≥1000 cases (or ≥20,000 participants for continuous factors), P < 0.05 in the largest study, 95% prediction interval excluding the null, and no large between-study heterogeneity, small study effects, or excess significance. Across the 57 topics, large heterogeneity was observed in the proportion of associations fulfilling various quantitative criteria. The quantitative criteria were mostly independent from one another. Across 62 associations assessed in both RCTs and in observational studies, 37.1% had effect estimates in opposite directions and 43.5% had effect estimates differing beyond chance in the two designs. Across 94 comparisons assessed in both MR and observational studies, such discrepancies occurred in 30.8% and 54.7%, respectively.Conclusions: Acknowledging that no gold-standard exists to judge whether an observational association is genuine, statistically significant results are common in observational studies, but they are rarely convincing or corroborated by randomized evidence. [ABSTRACT FROM AUTHOR]

Background: Estimating total body fat in public hospitals using gold-standard measurements such as air displacement plethysmography (ADP), deuterium oxide dilution, or dual-energy X-ray absorptiometry (DXA) is unaffordable, and it is challenging to use skinfold thickness. We aimed to identify the appropriate substitute marker for skinfold thickness to estimate total body fat in pregnant women and infants.Methods: The study is part of a prospective cohort study titled MAASTHI in Bengaluru, from 2016 to 19. Anthropometric measurements such as body weight, head circumference, mid-upper arm circumference (MUAC), and skinfold thickness were measured in pregnant women between 14 and 36 weeks of gestational age; while measurements such as birth weight, head, chest, waist, hip, mid-upper arm circumference, and skinfold thickness were recorded for newborns. We calculated Kappa statistics to assess agreement between these anthropometric markers with skinfold thickness.Results: We found the highest amount of agreement between total skinfold thickness and MUAC (Kappa statistic, 0.42; 95 % CI 0.38-0.46) in pregnant women. For newborns, the highest agreement with total skinfold thickness was with birth weight (0.57; 95 % CI 0.52-0.60). Our results indicate that MUAC higher than 29.2 cm can serve as a suitable alternative to total skinfolds-based assessments for obesity screening in pregnancy in public facilities. Similarly, a birth weight cut-off of 3.45 kg can be considered for classifying obesity among newborns.Conclusion: Mid-upper arm circumference and birth weight can be used as markers of skinfold thickness, reflecting total body fat in pregnant women and the infant, respectively. These two anthropometric measurements could substitute for skinfold thickness in low- and middle-income urban India settings. [ABSTRACT FROM AUTHOR]

Background: Bariatric surgery may be indicated in patients with nonalcoholic fatty liver disease (NAFLD) to achieve and maintain the degree of weight loss required to ensure therapeutic effects. However, bariatric surgery is still underrecognized in the treatment of NAFLD, including its inflammatory subtype, nonalcoholic steatohepatitis (NASH). Moreover, there is a lack of follow-up outcome data on different types of bariatric surgery in patients with NAFLD. This study aims to adequately assess the effect of bariatric surgery on NAFLD remission in obese patients.Methods: This prospective multicentre observational follow-up study will include 142 obese patients with NAFLD scheduled to undergo one of the following surgical procedures: sleeve gastrostomy, Roux-en-Y gastric bypass, and one anastomosis gastric bypass. The primary outcome is the complete remission rate of NAFLD one year postoperatively, which is defined by liver fat fraction < 5% on magnetic resonance imaging; the secondary outcomes includes (i) changes in NASH and liver fibrosis biopsy findings, (ii) changes in body weight and abdominal adipose weight, (iii) resolution of obesity-related comorbidities, and (iv) incidence of adverse events. A long-term follow-up related to this study will also be conducted.Discussion: This study will provide a necessary and preliminary foundation for the early identification and targeted treatment of patients with NAFLD who can be referred for bariatric surgery, as indicated for management of obesity and metabolic disease.Trial Registration: Clinicaltrials.gov: NCT04366999. Registered 21 April 2020. ( https://clinicaltrials.gov/ct2/show/NCT04366999 ). [ABSTRACT FROM AUTHOR]

Background: Yoga can reduce the risk of preterm delivery, cesarean section (CS), and fetal death. The aim of the present study was to investigate the effects of Yoga on pregnancy, delivery, and neonatal outcomes.Methods: This was a clinical trial study and using the random sampling without replacement 70 pregnant women entered Hatha Yoga and control groups according to the color of the ball they took from a bag containing two balls (blue or red). The data collection tool was a questionnaire pregnancy, delivery, and neonatal outcomes. The intervention in this study included pregnancy Hatha Yoga exercises that first session of pregnancy Yoga started from the 26th week and samples attended the last session in the 37th week. They exercised Yoga twice a week (each session lasting 75 min) in a Yoga specialized sports club. The control group received the routine prenatal care that all pregnant women receive.Results: The results showed that yoga reduced the induction of labor, the episiotomy rupture, duration of labor, also had a significant effect on normal birth weight and delivery at the appropriate gestational age. There were significant differences between the first and second Apgar scores of the infants.Conclusion: The results of the present study showed that Yoga can improve the outcomes of pregnancy and childbirth. They can be used as part of the care protocol along with childbirth preparation classes to reduce the complications of pregnancy and childbirth.Trial Registration: IRCT20180623040197N2 (2019-02-11). [ABSTRACT FROM AUTHOR]

Objective: Gestational trophoblastic disease (GTD) is a group of pregnancy-related disorders that arise from abnormal proliferation of placental trophoblast. Some patients with GTD develop hyperthyroidism, a rare but potentially life-threatening complication requiring early detection and management. Existing literature on hyperthyroidism in GTD is scant. This review aims to analyse the epidemiology, pathophysiology and management of this phenomenon. Methods: A comprehensive search of MEDLINE, EMBASE and Cochrane Library was performed to obtain articles that explored hyperthyroidism in GTD. A total of 405 articles were screened and 228 articles were considered for full-text review. We selected articles that explored epidemiology, pathophysiology and outcomes/management of hyperthyroidism in GTD. Results: The pathophysiology of hyperthyroidism in GTD is well-investigated. Placental trophoblastic tissue secretes excessive hCG, which is structurally similar to thyroid stimulating hormone and also has enhanced thyrotropic activity compared to normal hCG. The incidence and prevalence of hyperthyroidism in GTD varies worldwide, with lower rates associated with high uptake of early antenatal screening and early GTD detection. No clear risk factors for hyperthyroidism in GTD were identified. While hyperthyroidism can be definitively managed with surgical evacuation of the uterus, severe complications associated with hyperthyroidism in GTD have been reported, including thyroid storm-induced multi-organ failure, ARDS, and pulmonary hypertension. Conclusion: Early detection of GTD is critical to prevent development of hyperthyroidism and its associated complications. Hyperthyroidism should be recognised as an important perioperative consideration for women undergoing surgery for GTD, and requires appropriate management. Future studies should explore risk factors for hyperthyroidism in GTD, which may facilitate earlier identification of high-risk women. [ABSTRACT FROM AUTHOR]

Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing rapidly. It is nowadays recognized as the most frequent liver disease, affecting a quarter of global population and regularly coexisting with metabolic disorders such as type 2 diabetes, hypertension, obesity, and cardiovascular disease. In a more simplistic view, NAFLD could be defined as an increase in liver fat content, in the absence of secondary cause of steatosis. In fact, the clinical onset of the disease is a much more complex process, closely related to insulin resistance, limited expandability and dysfunctionality of adipose tissue. A fatty liver is a main driver for a new recognized liver-pancreatic α-cell axis and increased glucagon, contributing to diabetes pathophysiology. Main text: This review will focus on the clinical and pathophysiological connections between NAFLD, insulin resistance and type 2 diabetes. We reviewed non-invasive methods and several scoring systems for estimative of steatosis and fibrosis, proposing a multistep process for NAFLD evaluation. We will also discuss treatment options with a more comprehensive view, focusing on the current available therapies for obesity and/or type 2 diabetes that impact each stage of NAFLD. Conclusion: The proper understanding of NAFLD spectrum—as a continuum from obesity to metabolic syndrome and diabetes—may contribute to the early identification and for establishment of targeted treatment. [ABSTRACT FROM AUTHOR]

Background: Individual prediction of life expectancy in patients with spinal metastases from hepatocellular carcinoma (HCC) is key for optimal treatment selection, especially when identifying potential candidates for surgery. Most reported prognostic tools provide categorical predictions, and only a few include HCC-related factors. This study aimed to investigate the natural progression of the disease and develop a prognostic tool that is capable of providing individualized predictions. Methods: Patients with HCC-derived metastatic spinal disease were identified from a retrospective cohort of patients with spinal metastases who were diagnosed at Chiang Mai University Hospital between 2006 and 2015. Kaplain–Meier methods and log-rank tests were used to statistically evaluate potential factors. Significant predictors from the univariable analysis were included in the flexible parametric survival regression for the development of a prognostic prediction model. Results: Of the 1143 patients diagnosed with HCC, 69 (6%) had spinal metastases. The median survival time of patients with HCC after spinal metastases was 79 days. In the multivariable analysis, a total of 11 potential clinical predictors were included. After backward elimination, four final predictors remained: patients aged > 60 years, Karnofsky Performance Status, total bilirubin level, and multifocality of HCC. The model showed an acceptable discrimination at C-statistics 0.73 (95% confidence interval 0.68–0.79) and fair calibration. Conclusion: Four clinical parameters were used in the development of the individual survival prediction model for patients with HCC-derived spinal metastases of Chiang Mai University or HCC-SM CMU model. Prospective external validation studies in a larger population are required prior to the clinical implication of the model. [ABSTRACT FROM AUTHOR]

Background: Prognostication tools for early-stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT) are currently lacking. The purpose of this study was to develop and externally validate a nomogram to predict overall survival in individual patients with peripheral early-stage disease.Methods: A total of 587 NSCLC patients treated with biologically effective dose > 100 Gy10 were eligible. A Cox proportional hazards model was used to build a nomogram to predict 6-month, 1-year, 3-year and 5-year overall survival. Internal validation was performed using bootstrap sampling. External validation was performed in a separate cohort of 124 NSCLC patients with central tumors treated with SBRT. Discriminatory ability was measured by the concordance index (C-index) while predictive accuracy was assessed with calibration slope and plots.Results: The resulting nomogram was based on six prognostic factors: age, sex, Karnofsky Performance Status, operability, Charlson Comorbidity Index, and tumor diameter. The slope of the calibration curve for nomogram-predicted versus Kaplan-Meier-estimated overall survival was 0.77. The C-index of the nomogram (corrected for optimism) was moderate at 0.64. In the external validation cohort, the model yielded a C-index of 0.62.Conclusions: We established and validated a nomogram which can provide individual survival predictions for patients with early stage lung cancer treated with SBRT. The nomogram may assist patients and clinicians with treatment decision-making. [ABSTRACT FROM AUTHOR]

Background: Bone complications (pathologic fracture, spinal cord compression, surgery to bone and radiation to bone) are a common problem in patients with multiple myeloma (MM). We set out to provide insights into the real-world burden of bone complications in patients with newly diagnosed MM (NDMM).Methods: We conducted a retrospective review of medical charts of patients with NDMM whose disease had progressed following first-line treatment in the 3 months before data collection in 2016 in five European countries (France, Germany, Italy, Spain and the United Kingdom).Results: The aggregated study population included 813 patients. Bone pain commonly led to MM diagnosis (63%) and 74% of all patients had two or more bone lesions at initiation of first-line treatment. Furthermore, 26% of patients experienced a new bone complication between MM diagnosis and disease progression following first-line treatment, despite 75% of individuals receiving bisphosphonates. Most bone complications (52%) occurred in the period before initiation of first-line treatment (mean duration: 2.3 months) and more than half of patients (56%) who experienced a new bone complication were hospitalised. Analgesics were used more frequently in patients with bone complications than in those without them (76% vs 50%, respectively). Furthermore, 51% of patients had renal impairment by the time first-line treatment was started. Overall, 25% of patients did not receive bisphosphonates for prevention of bone complications and one in four of those with renal impairment at initiation of first-line treatment did not receive bisphosphonates.Conclusions: Bone complications are common in patients with NDMM. They are frequently associated with hospitalization and analgesic use. Data from this study, conducted in the era of novel anti-myeloma therapies and before the approval of denosumab for use in patients with MM, suggest that although most patients (75%) received bisphosphonates, use of anti-resorptive therapy for prevention of bone complications may be suboptimal in patients with NDMM, irrespective of renal function. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine whether physical activity volume and intensity in mid-childhood and early adolescence were associated with cardiometabolic risk factors at 13.5 years.Methods: Participants were recruited from the Mysore Parthenon observational birth cohort. At ages 6-10 and 11-13 years, volume and intensity of physical activity were assessed using AM7164 or GT1M actigraph accelerometers worn for ≥4 days, and expressed as mean counts per day and percentage time spent in light, moderate and vigorous physical activity according to criteria defined by Evenson et al. At 13.5 years, fasting blood samples were collected; lipids, glucose and insulin concentrations were measured and insulin resistance (HOMA) was calculated. Systolic and diastolic blood pressure were measured at the left arm using a Dinamap (Criticon). Anthropometry and bio-impedance analysis were used to assess body size and composition. Metabolic and anthropometric measures were combined to produce a metabolic syndrome risk score.Results: At 6-10 years, boys and girls respectively spent a median (IQR) of 1.1 (0.5, 2.0) % and 0.8 (0.4, 1.3) % of recorded time vigorously active. At 11-13 years, boys and girls respectively spent a median (IQR) of 0.8 (0.4, 1.7) % and 0.3 (0.1, 0.6) % of time vigorously active. All of the physical activity parameters were positively correlated between the 6-10 year and the 11-13 year measurements indicating that physical activity tracked from childhood to early adolescence. There were no associations between physical activity at 6-10 years and individual 13.5 year risk factors but % time vigorously active was inversely associated with metabolic syndrome score (B = -0.40, 95% CI -0.75, 0.05). Volume of physical activity at 11-13 years was inversely associated with 13.5 year HOMA and fat percentage and vigorous physical activity was associated with HOMA, fat percentage, sum of skinfolds, waist circumference and total: HDL cholesterol ratio. Vigorous physical activity was inversely associated with metabolic syndrome score (B = -0.51, 95% CI -0.94, -0.08).Conclusions: Volume and intensity of physical activity in early adolescence were negatively associated with metabolic and anthropometric risk factors. Interventions that aim to increase adolescent physical activity, especially vigorous, may prevent cardiometabolic disease in later life. [ABSTRACT FROM AUTHOR]

Background: Guidelines suggest that patients discontinue Clopidogrel at least 5 days prior to coronary artery bypass grafting (CABG). Those with acute coronary syndrome (ACS) are at high risk for myocardial infarction (MI) if not treated with dual antiplatelet therapy (DAPT). We sought to assess pre and post-operative outcomes of patients maintained on Clopidogrel and aspirin up to the time of surgery and compare them with those on aspirin alone.Methods: From the cardiac surgery database, 240 patients were retrospectively registered between January and May 2017. There were 126 patients with ACS who underwent CABG on DAPT (Clopidogrel group [CG]) and 114 patients who underwent elective CABG on aspirin alone (control). The CG received intraoperative prophylactic platelet transfusion (PPT). Demographics, comorbidities, and laboratory data were prospectively entered at the time of surgery and were subsequently retrieved for analysis. Per and postoperative findings were identified and compared between both groups.Results: The cohort consisted of 240 patients (mean age 61 years, 81.3% were male, SD ± 9.58). Patients in the CG were younger (Median 57 vs. 63, P-value 0.001), and with male predominance (86% versus 75%, P-value 0.028). In addition, they had less prevalence for diabetes and renal failure as compared to control (P-values 0.003, and 0.005, respectively). There were no significant differences between both groups in number of vessels grafts, duration of on-pump and aortic clamp. Hematologic laboratory data had also similar baseline values. The CG had similar bleeding rate, redo surgery and in-hospital death (P-values non-significant), however more infection and total hospital stay as compared to control (p-values 0.048 and 0.001).Conclusion: Patients who are at increased risk for MI can be maintained on DAPT up to the time of CABG because surgery is safe when patients are offered PPT. [ABSTRACT FROM AUTHOR]

Background: Low birth weight prevalence in Malaysia remains high. Socioeconomic background may lead to differences in physical activity and maternal nutritional status, which may play an important role in birth outcomes.Methods: This prospective cross-sectional study aimed to identify rural-urban differences in risk factors for low birth weight among women in Malaysia. Pregnant women at ≥20 weeks of gestation in urban and rural Malaysia (n = 437) completed questionnaires on sociodemographic characteristics and physical activity. Weight and middle-upper arm circumference were measured. Infant birth outcomes were extracted from medical records.Results: The overall prevalence of low birth weight infants was 6.38%. Rural women had more low birth weight infants than urban women (9.8% vs 2.0%, p = 0.03). Findings showed rural women were less sedentary (p = 0.003) and participated in more household/caregiving activities (p = 0.036), sports activities (p = 0.01) and less occupational activity (p < 0.001) than urban women. Logistic regression revealed that older age (OR = 1.395, 95% Cl = 1.053 to 1.846), low parity (OR = 0.256, 95% Cl = 0.088-0.747) and low middle-upper arm circumference (OR = 0.738, 95% Cl = 0.552 to 0.987) increased the risk of low birth weight infants in rural, but not in urban women.Conclusions: We observed differences in risk factors for low birth weight between urban and rural pregnant women. Age, malnutrition and low parity were risk factors for low birth weight among rural pregnant women. Our findings suggest that rural pregnant women with low nutritional status should be encouraged to monitor their middle-upper arm circumference consistently throughout pregnancy. Improving nutritional status in rural pregnant women may reduce the risk of low birth weight infants in this population. [ABSTRACT FROM AUTHOR]

Background: Detrimental exposures during pregnancy have been implicated in programming offspring to develop permanent changes in physiology and metabolism, increasing the risk for developing diseases in adulthood such as hypertension, diabetes, heart disease and obesity. This study investigated the effects of protein restriction on the metabolism of amino acids within the oocyte, liver, and whole organism in a rat model as well as effects on mitochondrial ultrastructure and function in the cumulus oocyte complex. Methods: Wistar outbred female rats 8–11 weeks of age (n = 24) were assigned to three isocaloric dietary groups, including control (C), low protein (LP) and low protein supplemented with folate (LPF). Animals were superovulated and 48 h later underwent central catheterization. Isotopic tracers of 1-13C-5C2H3-methionine, 2H2-cysteine, U-13C3-cysteine and U-13C3-serine were administered by a 4 h prime-constant rate infusion. After sacrifice, oocytes were denuded of cumulus cells and liver specimens were obtained. Results: Oocytes demonstrated reduced serine flux in LP vs. LPF (p < 0.05), reduced cysteine flux in LP and LPF vs. C (p < 0.05), and a trend toward reduced transsulfuration in LP vs. C and LPF. Folic acid supplementation reversed observed effects on serine flux and transsulfuration. Preovulatory protein restriction increased whole-body methionine transmethylation, methionine transsulfuration and the flux of serine in LP and LPF vs. C (p = 0.003, p = 0.002, p = 0.005). The concentration of glutathione was increased in erythrocytes and liver in LP and LPF vs. C (p = 0.003 and p = 0.0003). Oocyte mitochondrial ultrastructure in LP and LPF had increased proportions of abnormal mitochondria vs. C (p < 0.01 and p < 0.05). Cumulus cell mitochondrial ultrastructure in LP and LPF groups had increased proportions of abnormal mitochondria vs. C (p < 0.001 and p < 0.05). Preovulatory protein restriction altered oocyte expression of Drp1, Opa-1, Mfn1/2, Parl and Ndufb6 (p < 0.05) and Hk2 (p < 0.01), which are genes involved in mitochondrial fission (division) and fusion, mitochondrial apoptotic mechanisms, respiratory electron transport and glucose metabolism. Conclusions: Preovulatory protein restriction resulted in altered amino acid metabolism, abnormal cumulus oocyte complex mitochondrial ultrastructure and differential oocyte expression of genes related to mitochondrial biogenesis. [ABSTRACT FROM AUTHOR]

Background: The ZOHé study was a prospective, non-interventional, multicentre study in France to assess the use of biosimilar filgrastim Zarzio® (Sandoz filgrastim) in routine clinical practice in patients at risk of neutropenia-inducing chemotherapy (CT).Methods: Patients ≥ 18 years undergoing CT for a malignant disease and with a first prescription for Zarzio® were enrolled in two cohorts according to tumour type: solid tumour or haematological malignancy; results from the solid tumour cohort are reported here. Analyses primarily described the prescription and use of Zarzio® in current practice, and also included identification of factors linked to prescription for primary prophylaxis and comparison of Zarzio® use in relation to European Organisation for Research and Treatment of Cancer (EORTC) guidelines.Results: Responses were obtained from 125 physicians and 1179 patients with solid tumours, allowing robust statistical analysis of the data. Use of Zarzio® in clinical practice was relatively standardised and followed label indication. The patient profile was in line with EORTC guidelines for granulocyte colony-stimulating factor (G-CSF) febrile neutropenia (FN) prophylaxis, and the majority of patients had ≥ 1 EORTC factor(s) for increased risk of febrile neutropenia. Some patients (10.8%) received Zarzio® despite receiving CT regimens categorised in guidelines as low (< 10%) FN risk ('over prophylaxis'). Nearly half of patients' CT regimens did not have a recommended FN risk category. Zarzio® was commonly initiated as primary prophylaxis; initiation in Cycle ≥ 2 of the current line of CT was associated more with a history of neutropenia. The safety profile of Zarzio® was confirmed.Conclusions: Use of Zarzio® in routine clinical practice is generally in line with EORTC guidelines for prophylaxis of CT-induced neutropenia. Patient-related risk factors appear to be a stronger driver of clinicians' decision to initiate Zarzio® than CT risk category for FN. The intrinsic risk of FN associated with a specific CT protocol is often miscategorised by physicians. In contrast to earlier reports of underuse of G-CSF prophylaxis, over prophylaxis is observed in a small subgroup of patients with FN risk of < 10%. [ABSTRACT FROM AUTHOR]

Background: Prospective study protocols and registrations can play a significant role in reducing incomplete or selective reporting of primary biomedical research, because they are pre-specified blueprints which are available for the evaluation of, and comparison with, full reports. However, inconsistencies between protocols or registrations and full reports have been frequently documented. In this systematic review, which forms part of our series on the state of reporting of primary biomedical, we aimed to survey the existing evidence of inconsistencies between protocols or registrations (i.e., what was planned to be done and/or what was actually done) and full reports (i.e., what was reported in the literature); this was based on findings from systematic reviews and surveys in the literature.Methods: Electronic databases, including CINAHL, MEDLINE, Web of Science, and EMBASE, were searched to identify eligible surveys and systematic reviews. Our primary outcome was the level of inconsistency (expressed as a percentage, with higher percentages indicating greater inconsistency) between protocols or registration and full reports. We summarized the findings from the included systematic reviews and surveys qualitatively.Results: There were 37 studies (33 surveys and 4 systematic reviews) included in our analyses. Most studies (n = 36) compared protocols or registrations with full reports in clinical trials, while a single survey focused on primary studies of clinical trials and observational research. High inconsistency levels were found in outcome reporting (ranging from 14% to 100%), subgroup reporting (from 12% to 100%), statistical analyses (from 9% to 47%), and other measure comparisons. Some factors, such as outcomes with significant results, sponsorship, type of outcome and disease speciality were reported to be significantly related to inconsistent reporting.Conclusions: We found that inconsistent reporting between protocols or registrations and full reports of primary biomedical research is frequent, prevalent and suboptimal. We also identified methodological issues such as the need for consensus on measuring inconsistency across sources for trial reports, and more studies evaluating transparency and reproducibility in reporting all aspects of study design and analysis. A joint effort involving authors, journals, sponsors, regulators and research ethics committees is required to solve this problem. [ABSTRACT FROM AUTHOR]

Background: Palliative thoracic radiotherapy (PTR) can relieve symptoms originating from intra-thoracic disease. The optimal timing and fractionation of PTR is unknown. Time to effect is 2 months. The primary aim of this retrospective study was to investigate survival after PTR, hypothesizing that a significant number of patients received futile fractionated PTR. The secondary aim was to find prognostic factors to guide treatment decisions. Methods: Patients with non-small-cell lung cancer (NSCLC) planned for PTR in the period of 2010-2011 at the University Hospital of Copenhagen were included. We noted pathology, tumor, node and metastasis (TNM) classification of malignant tumors, stage, indication, start date, schedule for PTR, completed y/n, performance status (PS) and time of death. Analyses were performed as an intention-to-treat using Cox regression, Fishers exact test and Kaplan Meier. Results: A total of 159 patients were included. Median overall survival (OS) was 4.2 months. Sixteen patients (10%) did either not begin or finish PTR. Of these, eight (5%) died prior to or during PTR. Of the 151 patients receiving PTR, sixteen patients (11%) died within 14 days, thirty-three (22%) within 30 days and fifty (33%) within 2 months. PS 0-1 and squamous cell carcinoma were correlated with a better survival. Conclusions: Our study show that a significant number of patients who received PTR died before they could achieve optimal effect of the treatment. PS and histology were significant prognostic factors favoring PS 0-1 and squamous cell carcinoma. Based on our study, we suggest that patients with PS 0-1 should be considered for fractionated PTR whereas patients with PS ≥ 2 should be considered for high dose single fraction only or supportive palliative care. [ABSTRACT FROM AUTHOR]

Background: A key aspect of the design of randomised controlled trials (RCTs) is determining the sample size. It is important that the trial sample size is appropriately calculated. The required sample size will differ by clinical area, for instance, due to the prevalence of the condition and the choice of primary outcome. Additionally, it will depend upon the choice of target difference assumed in the calculation. Focussing upon the hip and knee osteoarthritis population, this study aims to systematically review how the trial size was determined for trials of osteoarthritis, on what basis, and how well these aspects are reported.Methods: Several electronic databases (Medline, Cochrane library, CINAHL, EMBASE, PsycINFO, PEDro and AMED) will be searched to identify articles on RCTs of hip and knee osteoarthritis published in 2016. Articles will be screened for eligibility and data extracted independently by two reviewers. Data will be extracted on study characteristics (design, population, intervention and control treatments), primary outcome, chosen sample size and justification, parameters used to calculate the sample size (including treatment effect in control arm, level of variability in primary outcome, loss to follow-up rates). Data will be summarised across the studies using appropriate summary statistics (e.g. n and %, median and interquartile range). The proportion of studies which report each key component of the sample size calculation will be presented. The reproducibility of the sample size calculation will be tested.Discussion: The findings of this systematic review will summarise the current practice for sample size calculation in trials of hip and knee osteoarthritis. It will also provide evidence on the completeness of the reporting of the sample size calculation, reproducibility of the chosen sample size and the basis for the values used in the calculation.Trial Registration: As this review was not eligible to be registered on PROSPERO, the summary information was uploaded to Figshare to make it publicly accessible in order to avoid unnecessary duplication amongst other benefits ( https://doi.org/10.6084/m9.figshare.5009027.v1) ; Registered January 17, 2017. [ABSTRACT FROM AUTHOR]

Trials has 10 years of experience in providing open access publication of protocols for randomised controlled trials. In this editorial, the senior editors and editors-in-chief of Trials discuss editorial issues regarding managing trial protocol submissions, including the content and format of the protocol, timing of submission, approaches to tracking protocol amendments, and the purpose of peer reviewing a protocol submission. With the clarification and guidance provided, we hope we can make the process of publishing trial protocols more efficient and useful to trial investigators and readers. [ABSTRACT FROM AUTHOR]

Background: Use of antiplatelet therapy shortly before stroke due to spontaneous primary intracerebral haemorrhage (ICH) is associated with higher case fatality in comparison to ICH without prior antithrombotic drug use. The PlAtelet Transfusion in Cerebral Haemorrhage (PATCH) trial aimed to assess the effect of platelet transfusion in patients presenting with ICH while using antiplatelet therapy. The main hypothesis of PATCH was that platelet transfusion would reduce death or dependence by reducing ICH growth.Methods/design: PATCH was a multicentre prospective, randomised, open, blinded endpoint (PROBE) parallel group trial, conducted at 60 hospitals in The Netherlands, Scotland and France. Forty-one sites enrolled 190 patients with spontaneous supratentorial ICH aged ≥18 years, who had used antiplatelet therapy for ≥7 days preceding ICH, if Glasgow Coma Scale was ≥8. Participants were randomised (1:1, with a secure web-based system using permuted blocks, stratified by study centre and type of antiplatelet therapy pre-ICH) to receive either platelet transfusion within 6 hours of symptom onset and 90 minutes of diagnostic brain imaging, or standard care without platelet transfusion. The primary outcome was modified Rankin Scale (mRS) score assessed blind to treatment allocation at 3 months after ICH. Planned secondary outcomes included ICH growth on brain imaging performed approximately 24 hours after randomisation, survival at 3 months, disability at 3 months scored using the Amsterdam Medical Centre linear disability score, heterogeneity of treatment effect on mRS and ICH growth according to presence of the computed tomography angiography spot sign, causes of poor outcome, and cost-effectiveness. Safety outcomes were transfusion reactions, thromboembolic complications, and serious adverse events occurring during hospitalisation. This statistical analysis plan was written without knowledge of the unblinded data.Trial Registration: The trial was registered with the Netherlands Trial Register on 29 April 2008 ( NTR1303 ). [ABSTRACT FROM AUTHOR]

Background: Efavirenz is a commonly prescribed antiretroviral drug that is largely well tolerated. However, seizure disorder is a rare side effect. Prompt identification and immediate replacement of efavirenz with an alternative drug would effectively stop the seizures. To the best of our knowledge, we present the first reported case in the literature of complex partial seizures arising due to efavirenz.Case Presentation: We report a case of a 33-year-old Nigerian man treated with an efavirenz-based antiretroviral regimen for human immunodeficiency virus infection. He presented with seizures soon after commencement of antiretroviral drugs. His magnetic resonance imaging results were unremarkable. His blood levels of sodium, glucose, urea, and creatinine were within normal limits. However, his electroencephalogram showed intermittent bursts of high-voltage sharp waves and spikes bilaterally over frontotemporoparietal regions, a finding consistent with complex partial seizures. His efavirenz plasma level was 209.55 μg/ml. His seizures stopped following a switch to a non-efavirenz-based regimen.Conclusions: This report brings to light the occurrence of complex partial seizures in patients on efavirenz. It also demonstrates the effective resolution of seizures when efavirenz treatment is replaced with a non-efavirenz-based regimen. [ABSTRACT FROM AUTHOR]

Background: Unacknowledged inconsistencies in the reporting of clinical trials undermine the validity of the results of the trials. Little is known about inconsistency in the reporting of academic clinical drug trials. Therefore, we investigated the prevalence of consistency between protocols and published reports of academic clinical drug trials.Methods: A comparison was made between study protocols and their corresponding published reports. We assessed the overall consistency, which was defined as the absence of discrepancy regarding study type (categorized as either exploratory or confirmatory), primary objective, primary endpoint, and--for confirmatory trials only--hypothesis and sample size calculation. We used logistic regression, χ(2), and Fisher's exact test.Results: A total of 282 applications of academic clinical drug trials were submitted to the Danish Health and Medicines Authority in 1999, 2001, and 2003, 95 of which fulfilled the eligibility criteria and had at least one corresponding published report reporting data on trial subjects. Overall consistency was observed in 39% of the trials (95% CI: 29 to 49%). Randomized controlled trials (RCTs) constituted 72% (95% CI: 63 to 81%) of the sample, and 87% (95% CI: 80 to 94%) of the trials were hospital based.Conclusions: Overall consistency between protocols and their corresponding published reports was low. Motivators for the inconsistencies are unknown but do not seem restricted to economic incentives. [ABSTRACT FROM AUTHOR]

Background: We herein report the first case of X-linked agammaglobulinemia (XLA) that underwent allogeneic stem cell transplantation using reduced intensity conditioning (RIC). We chronologically observed the reconstitution of humoral immunity in this case. Case presentation: The patient was a 28-year-old Japanese male with XLA who previously had life-threatening infectious episodes and was referred for the possible indication of allogeneic stem cell transplantation. After a thorough discussion within specialists from different backgrounds, we decided to perform allogeneic peripheral stem cell transplantation from his HLA-identical elder brother. Due to the non-malignant nature of XLA, we selected RIC consisting of fludarabine, cyclophosphamide, anti-thymocyte globulin, and 3 Gy of total body irradiation. Neutrophil engraftment was achieved on day 11 with complete donor chimerism. No major complications, except for stage 1 skin graft-versus-host disease, were observed. The patient was discharged on day 75 and has been followed as an outpatient without any infectious episodes for more than 500 days. Conclusions: Regarding immune reconstitution, CD19+ cells, IgA, and IgM, which were undetectable before allogeneic stem cell transplantation (allo-SCT), started to increase in number 10 days after allo-SCT and continued to increase for more than 1 year. Anti-B antibodies appeared as early as day 10. Total IgG levels decreased after the discontinuation of IgG replacement and spontaneously recovered after day 350. However, most anti-viral IgG titers, except EB virus-virus capsid antigen IgG, disappeared after the discontinuation of IgG replacement. A seasonal vaccination to influenza was performed on day 148, with neither anti-influenza type A nor type B being positive after the vaccination. The transient transfer of allergic immunity to orchard grass was observed. Similar Bruton's tyrosine kinase (BTK) expression levels in monocytes and B-cells were observed between the patient and healthy control. B-cells in the peripheral blood (PB) of the patient on day 279 showed sufficient proliferation after a CD40L and IL-21 or CD40L and CpG stimulation. Effective immunoglobulin production and class switching were also observed after a CD40L and IL-21 or CpG stimulation. Signal joint kappa-deleting recombination excision circles (sjKRECs) became positive 16 days post-SCT, increased to 6300 copies/µg DNA at 42 days, and were maintained at a high level thereafter. The recovery of T-cell receptor excision circles (TRECs) was slow, but became detectable 1 year post-hematopoietic stem cell transplantation (HSCT). [ABSTRACT FROM AUTHOR]

Background: Essential interventions can improve maternal and newborn health (MNH) outcomes in low- and middle-income countries, but their implementation has been challenging. Innovative MNH approaches have the potential to accelerate progress and to lead to better health outcomes for women and newborns, but their added value to health systems remains incompletely understood. This study's aim was to analyze the landscape of innovative MNH approaches and related published evidence.Methods: Systematic literature review and descriptive analysis based on the MNH continuum of care framework and the World Health Organization health system building blocks, analyzing the range and nature of currently published MNH approaches that are considered innovative. We used 11 databases (MedLine, Web of Science, CINAHL, Cochrane, Popline, BLDS, ELDIS, 3ie, CAB direct, WHO Global Health Library and WHOLIS) as data source and extracted data according to our study protocol.Results: Most innovative approaches in MNH are iterations of existing interventions, modified for contexts in which they had not been applied previously. Many aim at the direct organization and delivery of maternal and newborn health services or are primarily health workforce interventions. Innovative approaches also include health technologies, interventions based on community ownership and participation, and novel models of financing and policy making. Rigorous randomized trials to assess innovative MNH approaches are rare; most evaluations are smaller pilot studies. Few studies assessed intervention effects on health outcomes or focused on equity in health care delivery.Conclusions: Future implementation and evaluation efforts need to assess innovations' effects on health outcomes and provide evidence on potential for scale-up, considering cost, feasibility, appropriateness, and acceptability. Measuring equity is an important aspect to identify and target population groups at risk of service inequity. Innovative MNH interventions will need innovative implementation, evaluation and scale-up strategies for their sustainable integration into health systems. [ABSTRACT FROM AUTHOR]

Background: Large for gestational age infants have an increased risk of obesity, cardiovascular and metabolic complications during life. Knowledge of the key predictive factors of neonatal adiposity is required to devise targeted antenatal interventions. Our objective was to determine the fetal metabolic factors that influence regional neonatal adiposity in a cohort of women with previous large for gestational age offspring.Methods: Data from the ROLO [Randomised COntrol Trial of LOw Glycaemic Index in Pregnancy] study were analysed in the ROLO Kids study. Neonatal anthropometric and skinfold measurements were compared with fetal leptin and C-peptide results from cord blood in 185 cases. Analyses were performed to examine the association between these metabolic factors and birthweight, anthropometry and markers of central and generalised adiposity.Results: Fetal leptin was found to correlate with birthweight, general adiposity and multiple anthropometric measurements. On multiple regression analysis, fetal leptin remained significantly associated with adiposity, independent of gender, maternal BMI, gestational age or study group assignment, while fetal C-peptide was no longer significant.Conclusion: Fetal leptin may be an important predictor of regional neonatal adiposity. Interventional studies are required to assess the impact of neonatal adiposity on the subsequent risk of childhood obesity and to determine whether interventions which reduce circulating leptin levels have a role to play in improving neonatal adiposity measures. [ABSTRACT FROM AUTHOR]

Background: So-Cheong-Ryong-Tang (SCRT), a traditional Korean medicine containing eight species of medicinal plant, has been used to treat patients with bronchial asthma and allergic rhinitis for hundreds of years; however, its anti-cancer potential is poorly understood. The present study was designed to evaluate the apoptotic effect of SCRT against human non-small-cell lung cancer (NSCLC) A549 cells. Methods: The effects of SCRT on cell growth and viability were evaluated by trypan blue dye exclusion and 3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide (MTT) assays, respectively. Apoptosis was detected using 4,6-diamidino-2-phenyllindile (DAPI) staining, agarose gel electrophoresis and flow cytometry. The protein levels were determined by Western blot analysis. Caspase activity was measured using a colorimetric assay. Results: SCRT treatment resulted in significantly decreased A549 cell growth and viability by induction of apoptosis. SCRT induced the translocation of pro-apoptotic Bax to the mitochondria, mitochondrial membrane permeabilization, cytochrome c release from mitochondria to cytosol, and activated caspase-9 and caspase-3. SCRT also increased death receptor-associated ligands and enhanced the activation of caspase-8 and cleavage of its substrate Bid. However, the pan-caspases inhibitor significantly blocked the SCRT-induced apoptosis, suggesting that it is a caspase-dependent pathway. In addition, SCRT suppressed the phosphorylation of phosphoinositide 3-kinase (PI3K) and Akt, and treatment with a potent inhibitor of PI3K further increased the apoptotic activity of SCRT. Conclusions: These findings suggest that SCRT may play its anti-cancer actions partly through a suppression of the PI3K/Akt signal pathway in A549 cells, and further in vivo studies on the potential of SCRT for prevention and therapy of NSCLCs are warranted. [ABSTRACT FROM AUTHOR]